Priming Of Mice Research Articles

Role of major and minor histocompatibility antigens in the suppression of alloreactive cytotoxic responses induced by alloantigen pretreatment

We have recently shown that priming mice with allogeneic strain A spleen cells before immunizattion with (A × B)F 1 spleen cells strongly suppresses the cytotoxic T-lymphocyte (CTL) response directed against linked strain B allogantigens. This specific decrease in the CTL responses against the second immunizing alloantigen is associated with high CTL response against the first priming alloantigen. The suppression of CTL responses against the strain B alloantigens is, however, not due to killing of F 1 spleen cells by anti-A CTL, since it was observed after immunization of primed mice with a mixture of (A × B)F 1 and B cells. In the present study, attempts were made to determine the relative contribution of H-2 and minor histocompatibility background antigens towards induction of suppression. Our results demonstrate that priming and immunizing spleen cells have only to share H-2 antigens in order to induce a downregulation of CTL responses directed against the linked alloantigens. This indicates that immunity against H-2 antigens is sufficient to induce suppression. However, priming against minor histocompatibility antigens also induces suppression, but only if spleen cells used for priming and immunization share H-2 antigens with the recipient strain. Therefore, the suppression can be induced by priming with non-H-2 antigens but is H-2-restricted. This study has also demonstrated that suppression can be induced by intraperitoneal or subcutaneous administration of allogeneic cells.

Alloantigen pretreatment induces a down-regulation of the in vivo subsequent development of cytotoxic T lymphocytes directed against linked alloantigens.

In the present study, we describe a new regulatory system that influences the in vivo development of cytotoxic T lymphocytes (CTL) and that could be related to epitopic suppression. Epitopic suppression has been previously shown to occur when carrier-primed mice are subsequently immunized with a "new" epitope coupled to the priming carrier. The suppression specifically inhibited the antibody response to the "new" epitope without affecting the secondary antibody response to the carrier. In this report, using a carrier/hapten-carrier type of immunization protocol, we have demonstrated that a similar regulatory system could also affect the induction of CTL directed against allogeneic cells. Priming mice with an alloantigen 1 (carrier) inhibits the induction of alloantigen 2 (hapten)-specific cytotoxic responses when the alloantigen 2 is presented in association with the alloantigen 1 on an F1 stimulator cell (hapten-carrier conjugate). This has been demonstrated by the specific decrease of anti-H-2b or anti-H-2d CTL responses generated in C3H/He mice (H-2k) previously primed with, respectively, H-2d or H-2b spleen cells before immunization with F1 (H-2d x b) spleen cells. This suppression of the CTL responses against the second immunizing alloantigen is associated with a strong CTL response against the first priming alloantigen. The induction of the suppression is dependent on the dose of H-2d spleen cells administered before immunization with F1 spleen cells and is not related to antigen elimination since a strong suppression of the CTL response against H-2b antigens is shown following immunization with a mixture of F1 cells and H-2b-bearing cells of H-2d-primed animals.

The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives. III. Eradication of disseminated murine chronic leukemia cells by utilizing MDP hapten-reactive helper T-cell activity.

A previous paper has demonstrated that enhanced tumor-specific immunity could be induced by priming mice with Bacillus Calmette Guerin (BCG) and subsequently immunizing them with syngeneic tumor cells modified with BCG-cross-reactive muramyl dipeptide (MDP) hapten. The present study establishes a tumor-specific immunotherapy protocol for a murine chronic leukemia based on the above T-T cell collaboration between antitumor effector T cells and anti-MDP hapten helper T cells induced by BCG priming. BALB/c mice which had been primed to BCG were injected intravenously (i.v.) with viable, syngeneic BCL1 leukemia cells. One week later, these mice were immunized intraperitoneally (i.p.) with unmodified or MDP hapten-modified, 10,000 R X-irradiated BCL1 cells, followed by 4 booster immunizations at 5-day intervals. The administration of unmodified BCL1 tumor cells into BCG-primed mice failed to prevent them from tumor death due to the persistent growth of preinjected BCL1 cells. In contrast, the immunization of BCG-primed, BCL1 leukemia-cell-bearing mice with MDP-modified BCL1 cells resulted in a high growth inhibition of leukemia cells and protection of these mice from death by leukemia. It was also revealed that potent tumor-specific, T-cell-mediated immunity was generated in mice which survived in this immunotherapy model. Thus, these results indicate that administration of MDP hapten-modified, syngeneic leukemia cells into leukemia-bearing mice which have been primed with BCG results in potent tumor-specific, T-cell-mediated immunity attributable to preventing the growth of disseminated leukemic cells.

Immunoresponses to Neisseria meningitidis epitopes: in vivo analysis of immunocompetent cells involved in suppression of secondary response to phosphorylcholine

The immune response to phosphorylcholine (PC) antigens has been extensively studied in recent years. Neisseria meningitidis serogroup B M986 (NMB) was recently reported to induce a PC-specific plaque-forming cell (PFC) immuno-response in mice, a characteristic useful for the study of immunomodulating properties of N. meningitidis. With this technique, priming mice with low doses of NMB has been shown greatly to impair their ability, one month after priming, to mount an anti-PC response induced by NMB; this suppression is permanent, does not involve switching from IgM to another immunoglobulin class, transiently affects the T15 idiotype expression and is carrier specific. We report, based on an analysis of spleen cells from NMB-primed mice in an adoptive transfer model, that this suppression does not appear to be mediated by B lymphocytes nor does it seem to be under the direct control of T lymphocytes; rather, it involves radio-resistant cells. Additionally, our results show that NMB modulates the idiotype composition of the anti-phosphorylcholine response, probably by enhancing the expression of so called hapten-augmentable PFC. These results demonstrate that NMB can interfere effectively with the immune response in a variety of ways.

The effect of aging on the induction of experimental autoimmune thyroiditis.

The effect of age on the ability to elicit the various immune functions comprising experimental autoimmune thyroiditis in mice has been examined. Compared with young mice (2 to 3 mo), CBA/CaJ and A/J aged mice (20 to 30 mo) show a drastic reduction in their ability to develop circulating antibody after injection of mouse thyroglobulin (MTg) or mouse thyroid extract (MTE) in complete Freund's adjuvant (CFA). Delayed-type hypersensitivity responses were also depressed, as well as the ability of aged lymph node cells to proliferate in vitro to antigen and the ability of aged splenic T cells to function as helper cells for in vitro antibody production. However, after injection of these thyroid antigens in CFA, aged mice developed thyroid lesions either comparable to or only slightly less intense than those observed in young mice. The disparity between the levels of immune responses and thyroid lesions observed in aged mice can be explained by the greater susceptibility of aged thyroids to tissue damage, since transfer of identical numbers of Con A-activated MTE-primed young splenocytes to young and aged recipients results in a more severe thyroiditis in the aged recipients. Priming mice to MTE in CFA at 9 mo of age, at which time mice are responsive to MTE, did not enhance either T or B cell responsiveness to injection of MTE in CFA at 24 mo of age. Lymphocytes from MTE-injected aged mice also failed to transfer thyroiditis to young recipients after in vitro activation of the lymphocytes with Con A.

Alternatives to pristane priming for ascitic fluid and monoclonal antibody production

A variety of agents were compared to pristane for priming mice prior to ascitic fluid production. Incomplete Freund's adjuvant was found to be as good as or better than pristane for priming before hybridoma cell inoculation. Complete adjuvant was also useful while priming with proteose-peptone; thioglycollate, corn oil or mineral oil elicited only minimum amounts of ascitic fluid after hybridoma injection.

Immunoresponses to Neisseria meningitidis epitopes: Immunodulation by meningococcus B acts on more than one meningococcal surface epitope

Neisseria meningitidis group B strain M986 (serotypes 2a, 7) (NMB) elicits a specific primary antiphosphorylcholine immune response in mice but not a secondary response. The ability of other serotype and serogroup meningococci to induce similar primary responses in mice was studied, as was the immunogenicity of trinitrophenyl coupled NMB (TNP-NMB) in primary and secondary antitrinitrophenyl responses. Except for NMB, all other strains tested (three serogroup B and one serogroup A meningococcal strains) were found to be very poor phosphorylcholine immunogens. TNP-NMB, however, though proving to be a very good TNP antigen, was only a weak phosphorylcholine antigen. Priming NBF1 female mice with TNP-NMB one month or more before challenging them with the same antigen induced a strong depression of anti-TNP response in the subsequent challenge. However, this effect was not observed with Xid NBF1 male mice. Furthermore, priming mice with NMB weakly affected the anti-TNP response, but greatly depressed the antiphosphorylcholine response, after TNP-NMB challenge. In addition, whereas apparently only one TNP-specific B cell subpopulation was responding in unprimed mice challenged simultaneously with TNP-NMB and TNP-Ficoll (non-additive response), priming mice with NMB appeared to facilitate the independent activation of two different TNP-specific B cell subpopulations (additive response).

Studies on the recovery from tolerance to tumor antigens. II. Accelerated recovery of tumor-specific effector T cells in tolerant mice by applying T-T cell interaction mechanism.

C3H/He mice were injected i.v. with heavily X-irradiated syngeneic X5563 tumor cells three times at 4-day intervals. This regimen resulted in the abrogation of the potential to generate X5563 tumor-specific T cell-mediated immunity as induced by i.d. inoculation of viable X5563 tumor cells followed by surgical resection of the tumor, representing the tolerance induction. Although such a tumor-specific tolerant state was long-lasting, the recovery of anti-X5563 effector T cell responses was observed when the above ordinary immunization procedure was performed 6 months after the tolerance induction. The present study investigated whether the recovery from the tolerance can be accelerated by applying a helper-effector T-T cell interaction model in which enhanced anti-X5563 immunity is obtained by priming mice with BCG and by immunizing X5563 tumor cells modified with BCG cross-reactive MDP hapten (designated as L4-MDP) in the presence of anti-L4-MDP helper T cells preinduced with BCG. The results demonstrated that BCG-primed mice which received the tolerance regimen failed to generate anti-X5563 immunity when the ordinary immunization was performed 2 or 3 months after the tolerance induction. In contrast, the immunization of BCG-primed and X5563-tolerant mice with L4-MDP-coupled X5563 tumor cells at comparable timing to that of the ordinary immunization were capable of generating potent X5563-specific in vivo protective T cell-mediated immunity. As control groups, BCG-primed or unprimed tolerant mice did not develop anti-X5563 immunity when immunized with L4-MDP-uncoupled or L4-MDP-coupled tumor cells, respectively. These results indicate that immunization of BCG-primed, tumor-tolerant mice with L4-MDP-modified tumor cells results in accelerated recovery from the tumor tolerance.

Effects of the adjuvants SGP and Quil A on the induction of experimental autoimmune thyroiditis in mice

In the present study, two adjuvants, SGP and Quil A, were assessed for their ability to induce experimental autoimmune thyroiditis (EAT) in mice. SGP (a synthetic copolymer of starch, acrylamide, and sodium acrylate) and Quil A (a plant saponin) were compared with lipopolysaccharide (LPS) and complete Freund's adjuvant (CFA) given together with mouse thyroglobulin (MTg) for their ability to induce EAT in CBA/J mice. Immunization with MTg and LPS, MTg and CFA, or MTg with SGP was effective in inducing anti-MTg antibodies and histologic EAT, while MTg with Quil A was ineffective in inducing either anti-MTg antibodies or EAT. MTg with LPS was able to prime mice for the development of an in vitro spleen cell proliferative response to MTg while MTg with SGP or with Quil A was unable to prime spleen cells to proliferate detectably in response to MTg. MTg with LPS given in vivo primes CBA/J spleen cells for further activation by in vitro culture with MTg to transfer EAT to naive CBA/J recipients. MTg with SGP was also effective in priming CBA/J spleen cells for in vitro activation and transfer of EAT while MTg with Quil A was ineffective. The effective adjuvant activity of SGP and its lack of toxicity relative to LPS should make it a useful agent for further studies in murine models of EAT.

Antibody-defective, genetically susceptible CBA/N mice have an altered Salmonella typhimurium-specific B cell repertoire.

CBA/N mice, which express the X-linked immunodeficiency gene xid, are susceptible to Salmonella typhimurium. The basis for this susceptibility is currently unknown. However, previous studies (10) from this laboratory have provided evidence that susceptibility may be due to a defective anti-S. typhimurium antibody response. In that report we hypothesized that the defective antibody response may be a reflection of an altered S. typhimurium-specific B cell repertoire. In the studies described here, we have investigated this hypothesis using a modification of the in vitro splenic focus system. The frequency and characteristics of salmonella-specific B cells in normal, innately resistant, CBA/Ca mice have been compared with those of salmonella-susceptible, anti-S. typhimurium antibody-defective CBA/N mice. The results show that CBA/N mice express no primary or secondary S. typhimurium-specific B cell precursors after stimulation with an acetone-killed and dried (AKD) preparation of S. typhimurium strain TML. However, after three immunizations, the CBA/N tertiary frequency of 15.4 per 10(6) splenic B cells was similar to the primary precursor frequency in immunologically normal CBA/Ca mice, but 23-fold lower than the tertiary precursor frequency in CBA/Ca control mice. Moreover, CBA/N mice had an altered isotype distribution pattern after stimulation with AKD-TML. Greater than 70% of the tertiary CBA/N TML-specific B cells secreted IgG2, in contrast to either nonimmune or primed control mice. In addition, 80% of the CBA/N TML-specific B cells secreted only a single isotype, whereas the majority of B cells from primed normal mice secreted multiple isotypes. Fine specificity analysis of the TML-specific B cells indicated that the array of antigenic determinants to which CBA/N B cells could respond was restricted. Although the majority of primed CBA/Ca and primed CBA/N B cells were specific for LPS, the fine specificity pattern exhibited by CBA/N B cells was similar to that observed in unprimed normal mice, i.e., the vast majority were specific for the O antigen region of the LPS molecule. In contrast, a major portion of the LPS-specific B cells in primed CBA/Ca mice were directed against the KDO/lipid A region of the LPS molecule. Therefore, it appears that CBA/N mice lack or are unable to stimulate the B cell subset that predominates in primed, normal mice. Taken together, these studies indicate that the basis for susceptibility of CBA/N mice to S. typhimurium is multifactorial and suggests that the inability of some animals to respond to some infectious agents may be related to holes in their B cell repertoire.

Xenogeneic recognition of soluble and cell surface HLA class II antigens by proliferative murine T cells.

In order to characterize the murine anti-human xenogeneic mixed lymphocyte reactions (MLR), we studied T cell proliferative responses against various human lymphoid cells by immunization of mice either with cellular or purified HLA-DR antigens. Data presented here indicated that small amounts of soluble HLA-DR antigen were able to prime mice, and that the xenogeneic MLR depends on the expression of HLA class II antigens on the stimulating cells. Experiments using a mutant cell line clearly showed that HLA-DP molecules were also sufficient in eliciting a primary or a secondary xenogeneic MLR while no secondary proliferative response was obtained with cells expressing only HLA class I molecules. Using a large panel of human cells with various haplotypes, our results also showed that (a) nonpolymorphic determinants of HLA class II antigens trigger dominantly the murine T cells and (b) the xenogeneic response required I-E and L3T4 accessory molecules and was not inhibited with anti I-A and monomorphic anti-HLA class II antigen monoclonal antibodies. Altogether these results suggest that HLA class II antigens act as nominal antigens in triggering a murine anti-human proliferative response.

Primary murine immunoglobulin M responses to certain pneumococcal capsular polysaccharides consist primarily of anti-pneumococcal cell wall carbohydrate antibodies.

The antibody induced in mice immunized with a vaccine preparation of type 6 (Danish type 6A) pneumococcal capsular polysaccharide (S6) reacted with several chemically disparate pneumococcal capsular polysaccharides. Equivalent numbers of plaque-forming cells were observed when sheep erythrocytes coated with either S6, type 19 pneumococcal capsular polysaccharide (S19), or the pneumococcal cell wall carbohydrate (PnC) were used to detect the response to S6 or to S19. The addition of exogenous PnC to the plaquing mixtures of spleen cells from S6-, S19-, or PnC-immunized mice inhibited the appearance of most (greater than or equal to 85%) of the plaque-forming cells. Furthermore, the addition of monoclonal antibody specific for the dominant (TEPC 15) idiotype of anti-phosphorylcholine (a component of PnC) antibodies also inhibited the appearance of most of the plaque-forming cells. A suppressed S19 response was induced by priming mice with a low dose of S19 or PnC 3 days before immunization with an optimal dose of S19 (low-dose paralysis). These results demonstrated that most, if not all, of the antibody stimulated by these preparations of S6 and S19 was actually induced by and was specific for PnC.

Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation

A cytotoxic factor was induced in pertitoneal fluid by injection of OK-432 in mice which had been primed with OK-432. Two-step stimulation (priming and eliciting) was always necessary to induce the cytotoxic factor. OK-432-primed mice did not produce soluble cytotoxic factor spontaneously and no cytotoxic activity was detected in the mice treated by a single injection of OK-432 as an eliciting agent. This observation was also confirmed by in vitro experiments. Only when activated macrophages were incubated with OK-432 (or with lipopolysaccharide) was cytotoxin released into medium supernatant. High doses of OK-432 were required to prime mice for the production of cytotoxic factor, whereas a small amount was enough to elicit. The peritoneal cytotoxic factor obtained by OK-432 injection appears to be identical to tumor necrosis factor in the serum for the following reasons: (1) The two factors are similar in mode of cytotoxic action. (2) Both are produced from macrophages. (3) They are similar in physicochemical characteristics. (4) The cytotoxicity of the peritoneal cytotoxic factor was totally abolished by anti-TNF serum.

Augmentation of the antibody response by hapten help. II. Determination by many genes outside the MHC.

The purpose of the present work was to characterize the immune response (Ir) genes that influence augmentation of the antibody response by help with the hapten azobenzene-arsonate (ABA). Hapten help was measured as the augmentation in the plaque-forming cell (PFC) response to bovine gamma globulin (BGG) after priming mice with ABA conjugated to ovalbumin (OVA) and challenging subsequently with ABA-BGG. The first approach involved inbred mouse strains that were matched for H-2 but differed in their non-H-2 genetic backgrounds. B10.D2 mice were low responders even though they shared the H-2d haplotype with BALB/c and DBA/2 mice, which were high responders. C57BL/10 mice were high responders even though they shared the H-2b haplotype with C57BL/6, C3H.SW, and A.BY mice, all of which were strains that were low responders. The second approach was to identify any segregation of H-2 with the gene(s) encoding susceptibility to hapten help in the backcross generation. (BALB/c X C57BL/6) F1 hybrids were backcrossed to C57BL/6. The results showed no association with the major histocompatibility complex (MHC).

Specific IgM enhances and IgG inhibits the induction of immunological memory in mice.

The effect of priming mice with IgM anti-SRBC (sheep erythrocytes) together with SRBC or IgG anti-SRBC together with SRBC on the development and expression of memory cells was studied. Mice primed with specific IgM and SRBC showed a much more efficient secondary plaque-forming cell and serum antibody response after challenge with SRBC in an adoptive transfer system than did controls primed with SRBC only. The expression of this enhanced memory of IgM-primed spleen cells was counteracted by the high levels of internal IgG anti-SRBC (also the result of priming with IgM) when the mice, instead of being tested in adoptive transfers, were challenged directly. The antigen-specific feedback suppression of the primary antibody response by specific IgG antibodies was also seen to inhibit partially the development of memory cells. The suppressive effect on priming could be demonstrated both in adoptive transfer systems and after direct boost of the same mice that received the primary immunization. Both the IgM enhancement and the IgG suppression of memory cell development were antigen-specific, since no effect on the antibody response to a non-cross-reacting antigen, horse erythrocytes, was seen. The effect of these up- or down-regulations of immunological memory could be demonstrated after secondary injections as long as 90-280 days after priming.

Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene.

Inoculation of rabbits and mice with a vaccinia-rabies glycoprotein recombinant (V-RG) virus resulted in rapid induction of high concentrations of rabies virus-neutralizing antibodies and protection from severe intracerebral challenge with several strains of rabies virus. Protection from virus challenge also was achieved against the rabies-related Duvenhage virus but not against the Mokola virus. Effective immunization by V-RG depended on the expression of a rabies glycoprotein that registered proline rather than leucine as the eighth amino acid from its NH2 terminus (V-RGpro8). A minimum dose required for effective immunization of mice was 10(4) plaque-forming units of V-RGpro8 virus. beta-propiolactone-inactivated preparations of V-RGpro8 virus also induced high levels of rabies virus-neutralizing antibody and protected mice against intracerebral challenge with street rabies virus. V-RGpro8 virus was highly effective in priming mice to generate a secondary rabies virus-specific cytotoxic T-lymphocyte response following culture of lymphocytes with either ERA or PM strains of rabies virus.

Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma.

Antiviral and macrophage-priming activities in the supernatant medium of a subclone of a concanavalin A-stimulated mouse T-cell hybridoma were investigated. The two activities were associated with a molecular weight of approximately 50,000 and could not be separated by various approaches. Both activities were eliminated by a highly specific neutralizing antibody against mouse interferon-gamma, but not by antibody against interferon-alpha and -beta. The ratio of priming to antiviral activity in the hybridoma culture supernate was indistinguishable from the ratio obtained with mouse interferon-gamma prepared by recombinant DNA technology. It was concluded from these data that the priming activity in hybridoma culture supernates was attributable to interferon-gamma and that this mediator is one form of the lymphokine macrophage-activating factor. Interferon-gamma was greater than 800 times more efficient at priming mouse macrophages for tumor cell killing than was a mixture of interferon-alpha and -beta. This finding contributes to growing awareness that type II interferon may have greater immunoregulatory potential than type I interferons.

Suppressive effect of X-irradiated tumor cell presensitization on the induction of syngeneic tumor immunity: II. Opposite effects of intravenous administration of TNP-conjugated tumor cells on the development of antitumor and anti-TNP-self cytotoxic effector cells

A comparison was made of the effects of iv inoculation of trinitrophenyl (TNP)-conjugated syngeneic X5563 tumor cells on the development of anti-TNP-modified self (TNP-self) and anti-X5563 tumor-specific T-cell-mediated cytotoxic responses. Administration of syngeneic TNP-conjugated spleen cells or X-irradiated TNP-conjugated X5563 cells resulted in an appreciable augmentation in the generation of TNP-reactive cytotoxic effector cell activity as measured by subsequent in vitro sensitization with TNP-self. In contrast, iv inoculation with either TNP-modified or unmodified X-irradiated X5563 tumor cells did not prime mice for antitumor cytotoxic responses, but abolished the ability of mice to develop antitumor cytotoxic effector cells even after effective in vivo immunization with tumor cells. The possible mechanisms by which the suppression of antitumor cytotoxic response was induced by conditions which simultaneously induced an enhanced anti-TNP-self cytotoxic response are discussed.

Chemical enhancement of tumor immunogenicity.

C57BL/6 spleen cells immunized in vitro against syngeneic methylcholanthrene-induced sarcoma cells(MC-1 cells) modified with various chemical reagents show cytotoxic activity against unmodified MC-1 cells in a short-term 51Cr release assay, whereas unmodified MC-1 cells are nonimmunogenic. The effector cells cross-react widely with many other fibroblastic and epithelioid tumors, even those that are not H-2 matched, as well as with some nonneoplastic cells. Priming mice in vivo with a hapten leads to enhanced anti-tumor cytotoxicity developed by spleen cells from these mice immunized in vitro against tumor cells modified with the same hapten. Cytotoxic activity is largely, but not completely, removed by treatment with anti-theta serum and C. The existence of suppressor cells that can inhibit an anti-tumor response is demonstrasted in in vitro immunizations of mixtures of spleen cells from normal mice and mice primed with mitomyhcin-treated tumor cells, the latter suppressing the former.

Interferon priming. Effects on interferon messenger RNA.

The effects of priming mouse cells with interferon on the production of interferon and its mRNA were investigated. Interferon-treated (primed) mouse L929 cells produce 3 to 10 times more interferon than do nonprimed cells following induction with Newcastle disease virus. Interferon appears 2 to 4 h sooner in the primed cultures than in nonprimed cultures and interferon production by primed cells becomes resistant to inhibition by actinomycin D about 4 h sooner than interferon production in nonprimed cells. Interferon mRNA is detected in primed-induced cells about 2 h earlier than in nonprimed-induced cells. It reaches peak levels about 2 to 4 earlier in primed cells, but it also disappears sooner in primed cells. The total amounts of interferon mRNA isolated from primed-induced cells and nonprimed-induced cells were indistinguishable, by the methods utilized. Therefore, although primed cells can produce significantly more interferon and make interferon mRNA sooner than nonprimed cells, the total amount of interferon mRNA produced is apparently not increased, nor is its half-life prolonged in primed cells. Thus, enhanced interferon production in primed cells may result from enhanced efficiency of translation of interferon mRNA in the primed cells.